The objectives of our Center can be summarized as follows: Development and characterization of suitable animal models for the study of atherosclerosis with special emphasis on the production of the more advanced stages of atherosclerosis (fibrous and complicated plaques) and on lipid metabolism; studies on genetically controlled metabolic processes affecting plasma cholesterol homeostatis and mesenchymal susceptibility to atherosclerosis; investigation of the relationships between plasma cholesterol concentration, stage of lesion progression, and the regressibility of atherosclerosis as measured pathologically, chemically, and physiologically (evaluation of the vascular function of coronary and peripheral arteries); the effect of diets and drugs that lower plasma cholesterol concentration on the prevalence and extensiveness of cholelithiasis; studies on the pathogenetic mechanisms of lesion progression using a combined morphologic and metabolic approach; investigation of the interrelationships between lipid and connective tissue metabolism particularly as these processes relate to atherosclerosis progression and regression; studies on the structure and function of lipoproteins as affected by heredity and diet and the effect of individual lipoproteins on lesion development and arterial metabolism; nutritional studies using a novel approach which combines whole body sterol balance and the use of genetically defined nonhuman primates; studies on the mechanisms by which certain known risk factors exacerbate atherosclerosis; and, other research unit projects related to the central theme of the Center activities (such as enzymatic regulation of plasma cholesterol homeostasis).